5-[F]Fluoro-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-oxazolo[5,4-b]pyridine

The gradual development and worsening of dementia is a characteristic feature of Alzheimer’s disease (AD), and currently no cure is available for this ailment. Medications available to treat AD can only modify or delay the onset of this disease, and there are many ongoing preclinical and clinical studies to develop a suitable therapy to treat this condition (1). It is hypothesized (known as the amyloid cascade hypothesis) that accumulation of an amyloid precursor protein derivative, the β-amyloid protein (Aβ), in the brain is responsible for bringing about changes in the biochemical and cellular functions of the brain and leads to the progression and manifestation of AD (2). Therefore, the Aβ is believed to be a good biomarker for the detection of AD. Most earlier studies performed to investigate this disease used human post-mortem brains, and little is known about the early events that promote the development of AD or about how the formation and deposition of the Aβ contributes to the disease process (2). More recently, many noninvasive imaging probes that can be used with the various imaging modalities, have been developed and evaluated for the detection of early stage Aβ plaques; however, due to inadequate permeation across the blood–brain barrier and/or low binding to the Aβ aggregates, these agents were considered unsuitable for visualization of the Aβ plaques in the human brain (2). In an effort to develop imaging compounds that can be used for the visualization of Aβ plaques, investigators have produced and evaluated radiolabeled compounds that can be used with positron emission tomography (PET) (3). Among these, the C-labeled Pittsburg Compound-B ([C]PIB), which has been shown to bind specifically to Aβ deposits in post-mortem AD brains under conditions, is most commonly used to diagnose the condition, but the major limitation of using this probe is the short half-life of C ( = 20 min) and the requirement of an onsite cyclotron for the generation of this radionuclide (2, 3). AS a result, C-labeled tracers are not the most suitable for commercialization (4), and [C]PIB is not approved by the United States Food and Drug Administration (FDA) as a diagnostic imaging agent for the detection of AD. F-Labeled AV-45 ([F]AV-45), which has a = 110 min and has been developed, characterized, and evaluated for the detection of Aβ plaques, has been shown to be suitable for the identification of patients with AD, and the binding of this tracer in the brain of AD patients correlated well with the presence of Aβ plaques observed in this organ during post-mortem studies (5). However, [F]AV-45 is not approved by the FDA as yet for the detection of AD in patients. Although [F]AV-45 appears to be a promising agent for the noninvasive detection of Aβ plaques, it may not be suitable for the visualization of early-onset Aβ deposits because this tracer (and other similar agents) shows high uptake in the white matter of the brain (3, 5). In a continued effort to develop an imaging agent that is superior to those currently available for the detection of Aβ deposits, Hostetler et al. developed 5-[F]fluoro-2-(1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-oxazolo[5,4-b]pyridine ([F]MK-3328) and showed that it was a promising PET agent for the detection of Aβ plaques because it has a low uptake in the white matter and the cortical gray matter of the rhesus monkey brain (3).